The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine

A Population Pharmacokinetic Analysis of the STOP-PD

Simon J C Davies, Benoit H. Mulsant, Alastair J. Flint, Barnett S. Meyers, Anthony J. Rothschild, Ellen M. Whyte, Margaret M. Kirshner, Denise Sorisio, Bruce G. Pollock, Robert Bies

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and Objective: Clinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods. Methods: The Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline. Olanzapine was started at 2.5–5 mg/day and sertraline at 25–50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine and 200 mg/day for sertraline. Up to four olanzapine concentration samples were collected during the 12-week trial and 12-week continuation phase. We used NONMEM (Version VII) for population pharmacokinetic analysis, assessing effects of the covariates sex, African American origin, smoking, age, and sertraline co-administration. Results: Population pharmacokinetic analysis comprised 336 samples from 175 individuals. The structural model published by Bigos et al. was sufficient to describe the olanzapine data adequately: a one-compartment model with first-order absorption and elimination, using an additive residual error structure with the absorption rate constant fixed to 0.5. Sertraline co-administration significantly increased olanzapine apparent clearance (p 

Original languageEnglish (US)
Pages (from-to)1161-1168
Number of pages8
JournalClinical Pharmacokinetics
Volume54
Issue number11
DOIs
StatePublished - May 14 2015

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olanzapine
Sertraline
Pharmacokinetics
Depression
Drug Therapy
Population
Structural Models
Expert Testimony
African Americans
Antidepressive Agents
Antipsychotic Agents

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine : A Population Pharmacokinetic Analysis of the STOP-PD. / Davies, Simon J C; Mulsant, Benoit H.; Flint, Alastair J.; Meyers, Barnett S.; Rothschild, Anthony J.; Whyte, Ellen M.; Kirshner, Margaret M.; Sorisio, Denise; Pollock, Bruce G.; Bies, Robert.

In: Clinical Pharmacokinetics, Vol. 54, No. 11, 14.05.2015, p. 1161-1168.

Research output: Contribution to journalArticle

Davies, SJC, Mulsant, BH, Flint, AJ, Meyers, BS, Rothschild, AJ, Whyte, EM, Kirshner, MM, Sorisio, D, Pollock, BG & Bies, R 2015, 'The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine: A Population Pharmacokinetic Analysis of the STOP-PD', Clinical Pharmacokinetics, vol. 54, no. 11, pp. 1161-1168. https://doi.org/10.1007/s40262-015-0275-1
Davies, Simon J C ; Mulsant, Benoit H. ; Flint, Alastair J. ; Meyers, Barnett S. ; Rothschild, Anthony J. ; Whyte, Ellen M. ; Kirshner, Margaret M. ; Sorisio, Denise ; Pollock, Bruce G. ; Bies, Robert. / The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine : A Population Pharmacokinetic Analysis of the STOP-PD. In: Clinical Pharmacokinetics. 2015 ; Vol. 54, No. 11. pp. 1161-1168.
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